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Alpha-1-microglobulin (alpha-1-m) is a low molecular weight glycoprotein (mw 25-33 KD) that is filtered through the glomeruli and reabsorbed in the proximal parts of the renal tubules where it is catabolized. Normal ranges were established for alpha-1-m (100 healthy controls) in serum (20-42 mg/l) and urine (3.5-8 mg/l). Alpha-1-m was then measured in 341 urine samples whose protein pattern had been classified as 'pathologic' and 'normal' according to microelectrophoresis. Increased alpha-1-m concentrations were found in 266 out of 280 pathologic urines (5% false negative) and in 3 out of 61 normal urines (4% false positive). Beta-2-microglobulin (beta-2-m), total protein or protein test strips showed a poorer correlation to the electrophoretic results. Measurement of alpha-1-m is, therefore, the most sensitive of these methods for the detection of proteinuria. In 90 patients with low molecular weight proteinuria and either with or without renal insufficiency alpha-1-m concentrations were determined in both urine and serum. While all patients had elevated urinary alpha-1-m concentrations, increased serum values were only found in renal insufficiency (C<100 ml/min). Independently of these results, we were also able to establish that increased alpha-1-m levels are found at decreased glomerular filtration rates (C <70 ml/min). Pathologic alpha-1-m concentrations therefore only allow the conclusion of isolated tubular impairment when the GFR is greater than 70 ml/min. Data from 350 patients with various renal and hypertensive diseases showed that serum alpha-1-m is a more sensitive indicator of renal insufficiency, even in the so-called 'creatinine blind' range (60-100 ml/min) of the GFR than either creatinine or beta-2-m. [ABSTRACT FROM AUTHOR]